title: Photodynamic synovectomy using benzoporphyrin derivative in an antigen-induced arthritis model for rheumatoid arthritis.
abstract: Experimental photodynamic therapy (PDT) has recently been adapted for the treatment of inflammatory and rheumatoid arthritis. The biodistribution of benzoporphyrin derivative monoacid ring A (BPD-MA) and the effect of percutaneous light activation via intra-articular bare cleaved optical fibers was investigated using a rabbit-antigen-induced arthritis model. Qualitative evaluation of intra-articular photosensitizer clearance was performed with laser-induced fluorescence from 0 to 6 h following intravenous injection. The compound was rapidly taken up within the joint and then cleared steadily over the 6 h interval. Biodistribution was determined by fluorescence microscopy and spectrofluoroscopic extraction techniques 3 h following intravenous injection of 2 mg/kg BPD-MA. The biodistribution study demonstrated elevated levels of BPD-MA in synovium (0.35 microgram/g) and muscle (0.35 microgram/g). Fluorescence microscopy demonstrated presence of the compound within pathologic synovium but absence of the photosensitizer within meniscus, ligament, bone and articular cartilage. Tissue effects were evaluated histologically at 2 and 4 weeks posttreatment. BPD-MA-mediated PDT caused synovial necrosis in the region of light activation in 50% of treatment knees at 2 weeks and 43% at 4 weeks. No damage to nonpathologic tissues was observed. These studies indicate that selective destruction of synovium can be achieved by the light-activated photosensitizing agent BPD-MA without damage to articular cartilage or periarticular soft tissues. PDT needs to be further evaluated to optimize treatment parameters to provide for a new minimally invasive synovectomy technique.
authors.affiliation: Department of Orthopaedic Surgery, UC Davis Medical Center, Sacramento 95817, USA.
authors.forename: K B
authors.initials: KB
authors.lastname: Trauner
authors.forename: R
authors.initials: R
authors.lastname: Gandour-Edwards
authors.forename: M
authors.initials: M
authors.lastname: Bamberg
authors.forename: S
authors.initials: S
authors.lastname: Shortkroff
authors.forename: C
authors.initials: C
authors.lastname: Sledge
authors.forename: T
authors.initials: T
authors.lastname: Hasan
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000378:metabolism / Q000628:therapy*; D004195:Disease Models, Animal; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011166:Porphyrins / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011817:Rabbits; D013583:Synovial Membrane / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D013585:Synovitis / Q000628:therapy; D014018:Tissue Distribution
chemical_list: D017319:Photosensitizing Agents; D011166:Porphyrins; C504224:benzoporphyrin D